Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~

Cancer Cell Metabolism Gene Database

Cancer Cell Metabolism Gene DB

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	Gene Summary
	Phenotypic Information (metabolism pathway, cancer, disease, phenome)
	Mutations : SVs, CNVs, SNVs
	Gene expression: GE, Protein, DEGE, CNV vs GE
	Gene-Gene Network Information: Co-Expression Network, Interacting Genes & KEGG
	Pharmacological Information: Drug-Gene Network
	Cross referenced IDs

Gene Summary for ADCY3

Basic gene info.	Gene symbol	ADCY3
	Gene name	adenylate cyclase 3
	Synonyms	AC3
	Cytomap	UCSC genome browser: 2p23.3
	Genomic location	chr2 :25042038-25142055
	Type of gene	protein-coding
	RefGenes	NM_004036.3,
	Ensembl id	ENSG00000138031
	Description	AC-IIIATP pyrophosphate-lyase 3adenylate cyclase type 3adenylate cyclase type IIIadenylate cyclase, olfactive typeadenylyl cyclase 3adenylyl cyclase, type III
	Modification date	20141207
dbXrefs	MIM : 600291
	HGNC : HGNC
	Ensembl : ENSG00000138031
	HPRD : 02620
	Vega : OTTHUMG00000094765
Protein	UniProt: O60266 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ADCY3
	BioGPS: 109
	Gene Expression Atlas: ENSG00000138031
	The Human Protein Atlas: ENSG00000138031
Pathway	NCI Pathway Interaction Database: ADCY3
	KEGG: ADCY3
	REACTOME: ADCY3
	ConsensusPathDB
	Pathway Commons: ADCY3
Metabolism	MetaCyc: ADCY3
	HUMANCyc: ADCY3
Regulation	Ensembl's Regulation: ENSG00000138031
	miRBase: chr2 :25,042,038-25,142,055
	TargetScan: NM_004036
	cisRED: ENSG00000138031
Context	iHOP: ADCY3
	cancer metabolism search in PubMed: ADCY3
	UCL Cancer Institute: ADCY3
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of ADCY3 in cancer cell metabolism	1. Hong SH, Goh SH, Lee SJ, Hwang JA, Lee J, et al. (2013) Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway. Oncotarget 4: 1791-1803. pmid: 3858564. go to article

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Phenotypic Information for ADCY3(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: ADCY3
	Familial Cancer Database: ADCY3

* This gene is included in those cancer gene databases.

						.
Oncogene ¹	Tumor Suppressor gene ²	Cancer Gene Census ³	CancerGenes ⁴	Network of Cancer Gene ⁵	Significant driver gene in	Therapeutic Vulnerabilities in Cancer¹

cf) number; DB name
1 Oncogene; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
2 Tumor Suppressor gene; https://bioinfo.uth.edu/TSGene/,
3 Cancer Gene Census; http://www.nature.com/nrc/journal/v4/n3/abs/nrc1299.html,
4 CancerGenes; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
5 Network of Cancer Gene; http://ncg.kcl.ac.uk/index.php,
1Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
KEGG_PURINE_METABOLISM REACTOME_INTEGRATION_OF_ENERGY_METABOLISM

Others
OMIM	600291; gene.
Orphanet
Disease	KEGG Disease: ADCY3
	MedGen: ADCY3 (Human Medical Genetics with Condition)
	ClinVar: ADCY3
Phenotype	MGI: ADCY3 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: ADCY3

Mutations for ADCY3

* Under tables are showing count per each tissue to give us broad intuition about tissue specific mutation patterns.You can go to the detailed page for each mutation database's web site.

Structural Variants in COSMIC : go to COSMIC mutation histogram

- Statistics for Tissue and Mutation type

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- For Inter-chromosomal Variations

There's no inter-chromosomal structural variation.

- For Intra-chromosomal Variations

* Intra-chromosomal variantions includes 'intrachromosomal amplicon to amplicon', 'intrachromosomal amplicon to non-amplified dna', 'intrachromosomal deletion', 'intrachromosomal fold-back inversion', 'intrachromosomal inversion', 'intrachromosomal tandem duplication', 'Intrachromosomal unknown type', 'intrachromosomal with inverted orientation', 'intrachromosomal with non-inverted orientation'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
lung	ADCY3	chr2	25081092	25081092		chr2	25942209	25942209

cf) Tissue number; Tissue name (1;Breast, 2;Central_nervous_system, 3;Haematopoietic_and_lymphoid_tissue, 4;Large_intestine, 5;Liver, 6;Lung, 7;Ovary, 8;Pancreas, 9;Prostate, 10;Skin, 11;Soft_tissue, 12;Upper_aerodigestive_tract)

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows ADCY3 related fusion information.

Head Gene

Tail Gene

Accession

Gene_a

qStart_a

qEnd_a

Chromosome_a

tStart_a

tEnd_a

Gene_a

qStart_a

qEnd_a

Chromosome_a

tStart_a

tEnd_a

Other DBs for Structural Variants

Structural Variants in Ensembl: go to Ensembl Structural variation

Structural Variants in dbVar: go to dbVar

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Copy Number Variations in COSMIC : go to COSMIC mutation CNV/Expr

Mutation type/ Tissue ID

brca

cns

cerv

endome

haematopo

kidn

Lintest

liver

lung

ovary

pancre

prost

skin

stoma

thyro

urina

Total # sample

GAIN (# sample)

LOSS (# sample)

cf) Tissue ID; Tissue type (1; Breast, 2; Central_nervous_system, 3; Cervix, 4; Endometrium, 5; Haematopoietic_and_lymphoid_tissue, 6; Kidney, 7; Large_intestine, 8; Liver, 9; Lung, 10; NS, 11; Ovary, 12; Pancreas, 13; Prostate, 14; Skin, 15; Stomach, 16; Thyroid, 17; Urinary_tract)

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SNV Counts per Each Loci in COSMIC data : go to COSMIC point mutation

: Non-synonymous mutation, : Synonymous mutation, Circle size denotes number of samples.
Maximum mutation count=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=78)	Stat. for Synonymous SNVs (# total SNVs=43)

Stat. for Deletions (# total SNVs=2)	Stat. for Insertions (# total SNVs=0)
	There's no inserted snv.

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Top 10 SNVs Having the Most Samples in COSMIC data

* When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site,primary_histology,mutation(aa),pubmedID.

GRCh37 position	Mutation(aa)	Unique sampleID count
chr2:25095541-25095541	p.I241I	3
chr2:25141368-25141368	p.H163H	3
chr2:25044490-25044490	p.E1008V	2
chr2:25062857-25062857	p.G414W	2
chr2:25141412-25141412	p.A149T	2
chr2:25141245-25141245	p.V204V	2
chr2:25141434-25141434	p.Y141Y	2
chr2:25057470-25057470	p.D617D	2
chr2:25095482-25095482	p.S261L	2
chr2:25062756-25062756	p.A447A	2

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SNV Counts per Each Loci in TCGA data

: non-synonymous mutation, : synonymous mutation, Circle size denotes number of samples.
maximum mutation count=2

Point Mutation/ Tissue ID	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
# sample	3	4		16	2		6		2	1	1	8	6	2			9	7	1	15
# mutation	3	4		17	2		6		2	1	1	8	7	2			10	8	1	15
nonsynonymous SNV	2	2		9	2		4		2	1	1	5	6	2			1	6	1	10
synonymous SNV	1	2		8			2					3	1				9	2		5

cf) Tissue ID; Tissue type (1; BLCA[Bladder Urothelial Carcinoma], 2; BRCA[Breast invasive carcinoma], 3; CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], 4; COAD[Colon adenocarcinoma], 5; GBM[Glioblastoma multiforme], 6; Glioma Low Grade, 7; HNSC[Head and Neck squamous cell carcinoma], 8; KICH[Kidney Chromophobe], 9; KIRC[Kidney renal clear cell carcinoma], 10; KIRP[Kidney renal papillary cell carcinoma], 11; LAML[Acute Myeloid Leukemia], 12; LUAD[Lung adenocarcinoma], 13; LUSC[Lung squamous cell carcinoma], 14; OV[Ovarian serous cystadenocarcinoma ], 15; PAAD[Pancreatic adenocarcinoma], 16; PRAD[Prostate adenocarcinoma], 17; SKCM[Skin Cutaneous Melanoma], 18:STAD[Stomach adenocarcinoma], 19:THCA[Thyroid carcinoma], 20:UCEC[Uterine Corpus Endometrial Carcinoma])

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Top 10 SNVs Having the Most Samples in TCGA data

* We represented just top 10 SNVs. When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site, primary_histology, mutation(aa), pubmedID.

Genomic Position	Mutation(aa)	Unique sampleID count
chr2:25141412	p.G1047G	2
chr2:25062839	p.V420M	2
chr2:25043704	p.A149T	2
chr2:25048948	p.Q260R	1
chr2:25062800	p.F57F	1
chr2:25141819	p.E1088K	1
chr2:25042928	p.R885R	1
chr2:25050956	p.V722M	1
chr2:25095482	p.R453L	1
chr2:25045432	p.R259H	1

Other DBs for Point Mutations

Point Mutation Table of Ensembl: go to Ensembl variation table

Mutation of cBioPortal: go to cBioPortal's Cross-cancer alteration summary

Copy Number for ADCY3 in TCGA

* Copy number data were extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered on Jan-05-2015. Function ProcessCNAData in TCGA-Assembler package was used to obtain gene-level copy number value which is calculated as the average copy number of the genomic region of a gene.

cf) Tissue ID[Tissue type]: BLCA[Bladder Urothelial Carcinoma], BRCA[Breast invasive carcinoma], CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], COAD[Colon adenocarcinoma], GBM[Glioblastoma multiforme], Glioma Low Grade, HNSC[Head and Neck squamous cell carcinoma], KICH[Kidney Chromophobe], KIRC[Kidney renal clear cell carcinoma], KIRP[Kidney renal papillary cell carcinoma], LAML[Acute Myeloid Leukemia], LUAD[Lung adenocarcinoma], LUSC[Lung squamous cell carcinoma], OV[Ovarian serous cystadenocarcinoma ], PAAD[Pancreatic adenocarcinoma], PRAD[Prostate adenocarcinoma], SKCM[Skin Cutaneous Melanoma], STAD[Stomach adenocarcinoma], THCA[Thyroid carcinoma], UCEC[Uterine Corpus Endometrial Carcinoma]

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Gene Expression for ADCY3

Gene Expression in Cancer Cell-lines (CCLE)

* CCLE gene expression data were extracted from CCLE_Expression_Entrez_2012-10-18.res: Gene-centric RMA-normalized mRNA expression data.

Differential Gene Expression in Primary Tumors (TCGA)

* Normalized gene expression data of RNASeqV2 was extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered at Jan-05-2015. Only eight cancer types have enough normal control samples for differential expression analysis.
(t test, adjusted p<0.05 (using Benjamini-Hochberg FDR))

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CNV vs Gene Expression Plot

* This plots show the correlation between CNV and gene expression.

: Open all plots for all cancer types

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Gene-Gene Network Information

Co-Expressed gene's network Plot

* Co-Expression network figures were drawn using R package igraph. Only the top 20 genes with the highest correlations were shown.
Red circle: input gene, orange circle: cell metabolism gene, sky circle: other gene

: Open all plots for all cancer types


ADCY3,CD14,CD180,CSF2RA,DOK5,EDN3,GNLY, KIR2DL3,LIPG,MRGPRX3,NOS1,PAK3,PDE11A,PGA5, PTN,TGFBR2,TLR2,TMEM100,TMEM233,VNN1,XDH	ACVRL1,ADCY3,AEBP1,BMP1,C1R,C1S,C3, CALHM2,CNTNAP1,GLIS2,GNAI2,GRK5,ITGA5,MAN1C1, MFNG,PLXND1,SYDE1,TMEM119,TMEM173,TNFRSF1A,TNFRSF1B

ADCY3,ASB13,ASXL1,SPATA25,CEP250,DHX35,DNAJC5, GNG4,KCNAB2,TTI1,NCOA6,PHF20,POLR1A,RNF43, RPRD1B,STX16,TAF4,TBC1D16,TEX261,TRPC4AP,ZHX3	ADCY3,ARAP3,BICD1,FAM208B,C1QTNF1,CD276,CEP135, CEP164,CEP97,DDHD1,DPY19L3,ILF3,LOC100129387,MDC1, NTRK3,NUP188,R3HDM1,RFX7,TP53BP1,UBQLN4,URB1

Co-Expressed gene's Protein-protein interaction Network Plot

: Open all plots for all cancer types

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Interacting Genes (from Pathway Commons)

: Open all interacting genes' information including KEGG pathway for all interacting genes from DAVID

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Pharmacological Information for ADCY3

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	ChEMBL	CHEMBL2097167; -.
Organism-specific databases	PharmGKB	PA164741137; -.
Organism-specific databases	CTD	109; -.

Drug-Gene Interaction Network

* Gene Centered Interaction Network.

* Drug Centered Interaction Network.

DrugBank ID	Target Name	Drug Groups	Generic Name	Drug Centered Network	Drug Structure
DB00938	adenylate cyclase 3	approved	Salmeterol

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Cross referenced IDs for ADCY3

* We obtained these cross-references from Uniprot database. It covers 150 different DBs, 18 categories. http://www.uniprot.org/help/cross_references_section

: Open all cross reference information